The Early Life Course of Body Weight and Gene Expression Signatures for Disease

We examined the way body-weight patterns through the first 4 decades of life relate to gene expression signatures of common forms of morbidity, including cardiovascular disease (CVD), type 2 diabetes (T2D), and inflammation. As part of wave V of the nationally representative National Longitudinal Study of Adolescent to Adult Health (1997–2018) in the United States, mRNA abundance data were collected from peripheral blood (n = 1,132). We used a Bayesian modeling strategy to examine the relative associations between body size at 5 life stages—birth, adolescence, early adulthood, young adulthood, and adulthood—and gene expression–based disease signatures. We compared life-course models that consider critical or sensitive periods, as well as accumulation over the entire period. Our results are consistent with a sensitive-period model when examining CVD and T2D gene expression signatures: Birth weight has a prominent role for the CVD and T2D signatures (explaining 33.1% and 22.1%, respectively, of the total association accounted for by body size), while the most recent adult obesity status (ages 33–39) is important for both of these gene expression signatures (24.3% and 35.1%, respectively). Body size in all life stages was associated with inflammation, consistent with the accumulation model.